Retinoic Acid Mediates Visceral-Specific Adipogenic Defects of Human Adipose-Derived Stem Cells.

Bibliographic Details
Title: Retinoic Acid Mediates Visceral-Specific Adipogenic Defects of Human Adipose-Derived Stem Cells.
Authors: Kosuke Takeda, Sriram, Sandhya, Xin Hui Derryn Chan, Wee Kiat Ong, Chia Rou Yeo, Betty Tan, Seung-Ah Lee, Kien Voon Kong, Shawn Hoon, Hongfeng Jiang, Jason J. Yuen, Jayakumar Peruma, Agrawal, Madhur, Vaz, Candida, Jimmy So, Shabbir, Asim, Blaner, William S., Olivo, Malini, Weiping Han, Tanavde, Vivek
Source: Diabetes; May2016, Vol. 65 Issue 5, p1164-1178, 15p, 1 Diagram, 7 Graphs
Subject Terms: METABOLIC disorders, OBESITY complications, STEM cell research, GENE expression, TRETINOIN, PROTEIN metabolism, ADIPOSE tissues, ANTI-infective agents, BIOCHEMISTRY, BIOLOGICAL transport, CELL culture, CELL physiology, CELL receptors, CELLULAR signal transduction, COMPARATIVE studies, DNA, GENES, GENETIC research, HYDROCARBONS, PHENOMENOLOGY, RESEARCH methodology, MEDICAL cooperation, BARIATRIC surgery, PROTEINS, RESEARCH, RESEARCH funding, STEM cells, STILBENE, EVALUATION research, MORBID obesity, GENE expression profiling, CHEMICAL inhibitors, PHARMACODYNAMICS
Abstract: Increased visceral fat, rather than subcutaneous fat, during the onset of obesity is associated with a higher risk of developing metabolic diseases. The inherent adipogenic properties of human adipose-derived stem cells (ASCs) from visceral depots are compromised compared with those of ASCs from subcutaneous depots, but little is known about the underlying mechanisms. Using ontological analysis of global gene expression studies, we demonstrate that many genes involved in retinoic acid (RA) synthesis or regulated by RA are differentially expressed in human tissues and ASCs from subcutaneous and visceral fat. The endogenous level of RA is higher in visceral ASCs; this is associated with upregulation of the RA synthesis gene through the visceral-specific developmental factor WT1. Excessive RA-mediated activity impedes the adipogenic capability of ASCs at early but not late stages of adipogenesis, which can be reversed by antagonism of RA receptors or knockdown of WT1. Our results reveal the developmental origin of adipocytic properties and the pathophysiological contributions of visceral fat depots. [ABSTRACT FROM AUTHOR]
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Database: Complementary Index
More Details
ISSN:00121797
DOI:10.2337/db15-1315
Published in:Diabetes
Language:English